Establish the relation between mucosal adenyl cyclase activity and cAMP levels and cholera exotoxin-induced intestinal secretion. While it has been established that an elevation of mucosal cAMP is associated with cholera-induced intestinal secretion in man and experimental animals, it is necessary to show that the biochemical event (increased mucosal cyclic AMP) preceeds the physiological event (onset of intestinal secretion), before a cause and effect relation can be considered established. To date, this has not been done. Cholera toxin-induced secretion can be demonstrated 15-30 minutes after exposure to toxin and reaches a maximum rate by 2 hours whereas observations showing elevation of cAMP prior to onset of secretion have not been published. Determine if there are any differences between crypt and villus adenyl cyclase and their patterns of activation after exposure to cholera toxin. If our hypothesis that cholera induced secretion originates in the crypts of Lieberkuhn is correct, and if cAMP is the "second messenger" in the initiation of cholera secretion, it is expected that differences between crypts and villi in adenyl cyclase and its activation by cholera toxin may be found. Determine if a change in phosphorylation of mucosal protein can be detected in association with toxin-induced elevation of mucosal cAMP and if specific labeling can be detected, what cell fraction or fractions are preferentially labeled. Determine at what steps in the induction of secretion various inhibitors, e.g., cycloheximide and polymixin, act. In view of hypotheses presented above, it might be expected that the inhibition produced by polymixin might be associated with a failure to activate adenyl cyclase; whereas, the block imposed by cycloheximide might act at some step beyond the production of cAMP.